中性和酸性基胺酶在瘤亡因子信号传导中的功能二分法
K Wiegmann1, S Schütze, T Machleidt
1Institut für Medizinische Mikrobiologie und Hygiene, Technische Universität München, Federal Republic of Germany.
Cell
|September 23, 1994
概括
瘤亡因子 (TNF) 独立地激活两种类型的髓酶 (SMases). 这些酶产生胺,控制不同的信号通路,如NF-kappa B激活和蛋白质激酶信号.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传输的方法
- 生物化学 生物化学
背景情况:
- 胺作为生长因子受体信号通路中的关键的第二信使.
- 斯芬哥米耶利纳酶 (SMases) 是负责胺生产的酶.
- 瘤亡因子 (TNF) 受体信号传递涉及复杂的下游事件.
研究的目的:
- 研究中性 (N-) SMase和酸性 (A-) SMase在TNF受体信号传递中的不同作用.
- 阐明由不同类型的SMase产生的陶胺调节的特定信号通路.
- 为了确定N-SMase和A-SMase介导的途径之间是否存在交叉.
主要方法:
- 激活TNF受体55 (TNF-R55) 刺激SMase活动.
- 通过与膜相关的N-SMase和内体体A-SMase区分amid的产生.
- 评估下游信号事件,包括蛋白激酶激活,脂酶A2和NF-kappa B激活.
主要成果:
- 结合TNF受体,通过不同的受体域迅速激活N-SMase和A-SMase.
- N-SMase的激活导致胺生成,从而触发了以proline为导向的蛋白激酶和脂酶A2.
- 激活A-SMase会产生特定激活NF-kappa B. 的胺基.
- 在N-SMase和A-SMase信号通路之间没有观察到交叉对话.
结论:
- N-SMase和A-SMase通过TNF受体信号独立地被激活.
- 陶胺的下游效应取决于其生产地点 (拓).
- 这两个SMase通路控制TNF受体信号转导的不同且不重叠的方面.
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